title: Functional role of alpha7 nicotinic receptor in chronic neuropathic and inflammatory pain: studies in transgenic mice.
abstract: A growing body of evidence indicates that α7 nicotinic receptor subtypes play an important role in chronic inflammatory and neuropathic pain signaling. In the present study, we investigated the role of the endogenous α7 nicotinic receptors (nAChRs) signaling in pain and inflammation using transgenic mice. For that we evaluated pain-related behaviors in the α7 mutant mice (KO) and its complementary α7 hypersensitive mice (KI) expressing the L250T α7 nAChRs and their respective WT mice in acute, chronic inflammatory and neuropathic mouse models. α7 KO and KI mice showed no significant changes in pain responses evoked by acute noxious thermal and mechanical stimuli as compared with WT littermates. While α7 KO mice showed no alterations in thermal and mechanical allodynia compared to WT mice after chronic nerve injury in the CCI test, α7 KI mice showed a significant reduction in these pain-related responses. However, marked increase in edema, hyperalgesia, and allodynia associated with intraplantar CFA injection was observed in the α7 KO mice compared with the WT littermates. In contrast, α7 KI mice displayed lesser degree of hyperalgesia and allodynia after CFA injection. Finally, the ability of systemic nicotine to reverse already-developed mechanical allodynia produced by intraplantar CFA seen in WT mice was lost in the α7 KO animals. Overall, our results demonstrate that endogenous α7 nAChRs mechanisms play an important role in chronic inflammatory and neuropathic pain models. This provides an additional rationale for the utility of α7 nAChR agonists in the treatment of inflammatory and chronic pain.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Shakir D
authors.initials: SD
authors.lastname: Alsharari
authors.forename: Kelen
authors.initials: K
authors.lastname: Freitas
authors.forename: M Imad
authors.initials: MI
authors.lastname: Damaj
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Alpha7 nicotinic receptors; CFA; Chronic pain; Inflammation; KI; KO; Mice; Nicotine; WT; complete Freund's adjuvant; i.p.; intraperitoneal; knock-in; knock-out; nAChR(s); nicotinic acetylcholine receptor(s); wild-type